Phospholipids play critical roles in hormone sensitive adenylate cyclase systems. The adenylate cyclase from cat myocardium has been solubilized utilizing the nonionic detergent, Lubrol-PX. The membrane-bound adenylate cyclase is activated by the catecholamines, glucagon, histamine, thyroid hormone, and prostaglandins. Solubilization abolished hormone-responsiveness. The adenylate cyclase, freed of detergent by DEAE-cellulose chromatography, remains in a soluble state, unresponsive to hormones. The addition of pure phosphatidylserine restored the activation of adenylate cyclase by glucagon and histamine, but not catecholamines. Phosphatidylinositol restored the activation of adenylate cyclase by the catecholamines, isoproterenol, epinephrine, and norepinephrine and was associated with an increase in sensitivity of the enzyme for the catecholamines. Solubilized preparations of cardiac adenylate cyclase in the presence and absence of detergent have the capacity to bind I125-glucagon and 7-H3-D,L-norepinephrine. The binding reaction is unaffected by the addition of phospholipids providing evidence for a dissociation of binding of hormone to receptors and activation of adenylate cyclase. Prostaglandins activate the solubilized enzyme independent of any phospholipid suggesting that prostaglandins act in the manner of phospholipids. In the present studies we will attempt to purify the various cardiac hormone receptors by such techniques as affinity chromatography, and gel electrophoresis. The fetal development of cardiac hormone receptors will be investigated and a comparative study of beta adrenergic receptors in different tissues undertaken. Furthermore, we will study the role of hormones on the metabolism of acidic phospholipids in cardiac membranes in both the normal and failure heart. Other studies include the effect of phospholipids on the glucagon unresponsiveness of adenylate cyclase from failure hearts and the purification and isolation of the cardiac prostaglandin receptor.